The long-term objectives of our research program are to create a model of how mental stress causes myocardial ischemia in patients with coronary disease (CAD), and to use this model to test treatments that improve prognosis for the approximately 50% of CAD patients who are at risk for poor outcomes because of mental stress provoked ischema. The Specific Aims of this application concern autonomic, inflammatory, and vascular pathways that are intermediary between the central nervous system and cardiovascular system and that we believe play a key role in mental stress ischemia. We aim to tie our prior observations regarding brain activity and myocardial blood flow during mental stress by, 1) assessing key intermediary autonomic pathways during mental stress in patients with CAD, and 2) determining the contributions of dispositional (hostility) and reactive factors (state anger) to the provocation of ischemia during mental stress. We will test hypotheses regarding, a) changes in autonomic tone, accompanying increases in levels of proteins that affect the functioning of blood vessels, and patterns of brain activity caused by mental stress and resulting in mental stress ischemia; and, b) the relationship of hostility and anger in the prediction of mental stress ischemia and the prediction of changes in autonomic tone, increases in levels of proteins that affect the functioning of blood vessels, and patterns of brain activity caused by mental stress. PUBLIC HEALTH RELEVANCE: Mental Stress Ischemia contributes to poorer prognosis in patients with coronary disease. The complete modeling of this ischemia, which is the focus of this application, will help efforts to define and test treatments aimed at reducing the risk of mental stress ischemia and improve medical outcomes for patients with coronary disease. [unreadable] [unreadable] [unreadable]